LXR激动剂TO901317对成年小鼠海马齿回星形胶质细胞的作用

Effect of liver X receptor agonist TO901317 on astrocyte in hippocampal dentate gyrus in adult mice

目的观察肝脏X受体(liver X receptor,LXR)激动剂TO901317对成年小鼠海马齿回(dentate gyrus,DG)星形胶质细胞数量以及海马齿回颗粒下区(dentate gyrus subgranular zone,DG-SGZ)星形胶质细胞放射状突起的作用。方法 3个月龄健康雄性C57B/L6小鼠采用TO901317激动剂灌胃1周,采用免疫组化检测小鼠海马星形胶质细胞的数量和形态学变化,采用RT-PCR检测海马LXRα、LXRβ、Klf-9、ABCA1、ABCG1和apoE的表达。测量肝脏大小和质量。结果 TO901317激动剂灌胃1周后,海马齿回胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)阳性的星形胶质细胞数量显著减少(P<0.05),而海马DG-SGZ区GFAP阳性的放射状纤维显著增多(P<0.01);小鼠海马LXRα表达无显著变化(P>0.05),而LXRβ表达显著下降(P<0.05),Klf-9、ABCA1、ABCG1和apoE表达显著升高(P<0.05)。灌注TO901317后小鼠肝脏显著肿大,质量较DMSO对照组显著增加(P<0.01)。结论 TO901317通过LXRβ受体调节Klf-9、ABCA1、ABCG1、apoE的表达,从而显著增加海马神经发生区GFAP长纤维的延伸。

Objective To determine the effect of TO901317,the agonist of liver X receptor,on the number of astrocytes in hippocampal dentate gyrus（DG） and on radial processes in the dentate gyrus subgranular zone（DG-SGZ） in adult mice.Methods TO901317（40 mg/kg） was intragastrically administrated to the healthy female C57B/L6 mice for 7 d.The number of GFAP positive cells and radial-like fibers in the hippocampus was detected by immunohistochemistry.The expression of LXRα,LXRβ,Klf-9,ABCA1,ABCG1 and apoE was detected by RT-PCR.The size and weight of the liver were also observed.Results After 1 week＇s TO901317 treatment,the number of GFAP positive cells in the DG was decreased markedly（P0.05）,while the GFAP positive radial-like fiber in the SGZ was increased significantly（P0.01）.No change was found in the expression of LXRα,while that of LXRβ was decreased（P0.05）.The expression of Klf-9,ABCA1,ABCG1 and apoE was increased significantly after TO901317 administration（P0.05）.Significant increases of the liver size and weight were observed in TO901317 group when compared with those in DMSO group（P0.01）.Conclusion Through LXRβ receptor,TO901317 modulates the expression of Klf-9,ABCA1,ABCG1 and apoE,and improves the outgrowth of radial-like process of astrocytes in the DG-AGZ.